ImmuRx is developing a novel and potent immunotherapeutic product to stimulate the immune system. This will significantly increase the efficacy of existing and new therapeutic vaccines for the treatment of cancers such as melanoma, lymphoma and lung cancer and for chronic infectious diseases such as Hepatitis C. The barrier to the induction of protective, therapeutic immunity to cancer antigens has been the inability to create vaccines that can elicit very high numbers of tumor-reactive T cells in the cancer and patient microenvironment. The innovative ImmuRx approach takes advantage of the novel and patented synergistic impact resulting from the combined adjuvant activity of two different immune system activators, a CD40 agonist and IFN-(2b or a Toll-like receptor agonist (TLR*). ImmRx's unique approach is that the combination therapy activates both the adaptive and innate immune system in vivo, as opposed to the approach of stimulating effector T cell expansion ex vivo, and this will leads to a long lasting and effective immunity. Further, it provides a much more effective means of stimulating protective immunity in patients compared to single agent products. CD40 agonists, TLR agonists, and IFN( have all been tried separately in the clinic for treatment of immune-responsive cancers and the results have generally been disappointing. INtron(r) A (IFN-(2b) is a commercially available therapeutic used to treat patients with advanced/high-risk melanoma, but use of this product has resulted in marginal survival gains at best and at a cost of significant toxicity. ImmuRx has demonstrated a significant increase in antigen-specific T cell activation in murine models. Given this potent impact on immune function, we expect this product will provide a breakthrough that may finally unlock the potential of active immunotherapy for a wide variety of cancers and chronic infectious disease. The competitive advantage of the ImmuRx platform has been demonstrated in animal testing in solid tumors, hematologic cancers and infectious disease. The initial therapeutic target for ImmuRx's product is advanced melanoma, a devastating cancer that has a low but reproducible response to immunomodulatory agents. This validates the use of ImmuRx's active vaccine approach for this disease. IFN-(2b as a single agent is approved for treatment of Stage III melanoma, but has marginal effect on the overall survival. ImmuRx's adjuvant platform and vaccine technology will provide clinicians with a significant improvement over IFN-( monotherapy, enabling a single treatment to stimulate high frequencies of tumor-specific effector T cells and to increase tumor regression in late stage melanoma. The funding requested for this SBIR Phase II award will be used to perform step-wise and sequential IND-enabling activities that will propel this exciting technology towards the clinic and its eventual approval for use in the treatment of cancers in humans. PUBLIC HEALTH RELEVANCE: ImmuRx is developing a novel and powerful immunotherapeutic product to stimulate the immune system. This will significantly increase the efficacy of existing and new therapeutic vaccines for treatment of cancers such as melanoma, lymphoma and lung cancer and for chronic infectious diseases such as Hepatitis C. The product will consist of a single injection that will increase both types of immune system function and will provide a long lasting and effective response. The initial product will be developed and tested for efficacy in advanced melanoma. This proposal requests funding for development activities that will enable ImmuRx to move the product towards eventual human clinical evaluation but does not request funding for clinical trials.